Tumor-suppressive activity of sTRAIL on circulating CD44+ cells in patients with non-small cell lung cancer

Biol Chem. 2020 Feb 25;401(3):417-422. doi: 10.1515/hsz-2019-0339.

Abstract

Circulating CD44+ cells have been identified as a prognostic marker for patients with non-small cell lung cancer (NSCLC). Serum tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) is involved in the pathophysiology of many cancers. However, no previous studies have shown the roles of sTRAIL in circulating CD44+ cells in the blood of NSCLC patients. We detected circulating CD44+ cells and sTRAIL levels in blood samples from NSCLC patients using flow cytometry and an enzyme-linked immunosorbent assay (ELISA). Anti-tumor roles of TRAIL in CD44+ cells were confirmed using a CCK-8 assay and mouse models. A higher number of circulating CD44+ cells were identified in NSCLC patients compared with healthy control individuals. In addition, we confirmed the anti-tumor roles and mechanisms of TRAIL in CD44+ cells both in vitro and in vivo. Our results indicate that (1) there is a negative correlation between sTRAIL and circulating CD44+ cells in NSCLC patients and (2) CD44+ cells have cancer stem cell properties and are more sensitive than CD44- cells to TRAIL.

Keywords: CD44; NSCLC; P53; TRAIL; prognosis.

MeSH terms

  • Animals
  • Carcinoma, Non-Small-Cell Lung / blood
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Humans
  • Hyaluronan Receptors / blood
  • Hyaluronan Receptors / metabolism*
  • Lung Neoplasms / blood
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Mice
  • TNF-Related Apoptosis-Inducing Ligand / blood
  • TNF-Related Apoptosis-Inducing Ligand / metabolism*

Substances

  • CD44 protein, human
  • Hyaluronan Receptors
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human